Crystallography and NMR: Applications to Organic and Pharmaceutical Chemistry

Potrzebowski, Marek J.

doi:10.1002/9780470034590.emrstm1005

Cited by 6 publications

(4 citation statements)

References 75 publications

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“…NMR has been widely used to study the rich polymorphism that is often found for molecular systems, as the chemical shift is a very sensitive probe of the local environment (including both the covalent bonds that are formed and the spatial proximity of other nuclei). [221][222][223][224][225][226] As such, this can provide information not just on molecular structure (as in solution-state NMR) but also on the spatial arrangement of molecules in the solid state (i.e., the crystal packing), and the number of distinct molecules within a structure. Figure 22a shows 13 C CP MAS spectra of two forms of finasteride.…”

Section: Molecular Systemsmentioning

confidence: 99%

Exploiting NMR spectroscopy for the study of disorder in solids

Moran

Dawson

Ashbrook

2017

International Reviews in Physical Chemistry

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Although the solid state is typically characterised by inherent periodicity, many interesting physical and chemical properties of solids arise from a variation in this, i.e., changes in the nature of the atom occupying a particular site in a crystal structure or variation in the position of an atom (or group of atoms) in different parts of a structure, or variation as a function of time. This lack of long-range order poses significant challenges, not just for the characterisation of the structure of disordered materials, but also simply for its description. The sensitivity of nuclear magnetic resonance (NMR) spectroscopy to the local, atomic-scale environment, without the requirement for long-range order, makes it a powerful tool for the study of disorder in the solid state. Information on the number and type(s) of coordinating atoms or through-space and through-bond connectivity between atomic species enables the construction of a detailed picture of the structure. After a brief description of the background theory of NMR spectroscopy, and the experimental methods employed, we will describe the effects of disorder on NMR spectra and the use of calculations to help interpret experimental measurements. We will then review a range of applications to different types of disordered materials, including oxides and ceramics, minerals, porous materials, biomaterials, energy materials, pharmaceuticals, polymers and glasses. We will discuss the most successful approaches for studying different materials, and illustrate the type of information available and the structural insight gained.

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Section: Molecular Systemsmentioning

confidence: 99%

Exploiting NMR spectroscopy for the study of disorder in solids

Moran

Dawson

Ashbrook

2017

International Reviews in Physical Chemistry

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“…SSNMR was also functional to detect the crystal form present in Difmetré (film-coated tablet). In this regard, and especially for pharmaceutical solids, we note that SSNMR is well suited to investigate the intermolecular interactions that dictate crystal packing, such as HB and π-stacking, in both pure form and in formulations. − More importantly, SSNMR has long been used to elucidate the crystal packing interactions in polymorphs − and cocrystals of IND. , …”

Section: Introductionmentioning

confidence: 99%

Engineering Codrug Solid Forms: Mechanochemical Synthesis of an Indomethacin–Caffeine System

Bordignon

Vioglio

Priola

et al. 2017

Crystal Growth & Design

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This article reports on the preparation and solid-state characterization of an indomethacin–caffeine drug–drug cocrystal (or codrug) in a 1:1 stoichiometry. These two active ingredients are frequently coadministered as part of a therapy against strong migraines, in a commercially available fixed dose combination formulation. The X-ray crystal structure of the codrug is characterized by a hydrogen bond interaction between the carboxylic moiety of indomethacin and the purinic nitrogen atom of caffeine. The combination of multinuclear and multidimensional solid-state NMR measurements (1H MAS, 13C and 15N CPMAS, 1H DQ MAS, 13C–1H HETCOR, 14N–1H J- and D-HMQC), as well as IR data, provided spectroscopic evidence about the hydrogen atom position along the hydrogen bond axis, thereby confirming the neutral nature of the cocrystal. Furthermore, dissolution kinetic tests revealed superior bioavailability of indomethacin in the codrug compared to indomethacin alone and to an indomethacin–caffeine physical mixture. On the other hand, the melting point of indomethacin was slightly lower in the cocrystal rather than in the pure drug.

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“…Solid-state NMR is a powerful tool for studying polymorphism of organic molecular solids, especially pharmaceuticals. − Most solid-state NMR studies of pharmaceutical molecules have employed 1 H and 13 C as NMR probes because of the ease in obtaining NMR signals from these nuclei at their natural abundance levels. However, recent studies have shown that, with isotopic 17 O-labeling, it is possible to obtain solid-state 17 O NMR spectra for organic and biological molecules and use them to complement the 1 H and 13 C NMR data for these molecules. − In principle, one should be able to obtain more complete information about molecular structure and bonding by studying all magnetic nuclei available in a molecule such as 1 H, 13 C, and 17 O.…”

Section: Introductionmentioning

confidence: 99%

Solid-State ¹H, ¹³C, and ¹⁷O NMR Characterization of the Two Uncommon Polymorphs of Curcumin

Dai

Terskikh

Brinmkmann

et al. 2020

Crystal Growth & Design

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Curcumin is known to exist in three polymorphs (forms I, II, and III) in the solid state. The most common polymorph of curcumin (form I) is monoclinic in the space group P2/n, whereas the other two uncommon forms are both orthorhombic with the space groups of Pca21 and Pbca for forms II and III, respectively. While crystal structures are known for all three polymorphs of curcumin, their solid-state NMR signatures are incomplete in the literature. In this study, we report a complete set of solid-state 1H, 13C, and 17O NMR data for form III of curcumin. In addition, we discovered that form III of curcumin prepared by repeated drying from methanol is not stable, which undergoes slow structural transition to form II in the solid state over a period of days at room temperature. As a result, we were able to obtain new solid-state 17O NMR data for form II of curcumin, which complements the existing solid-state 1H and 13C NMR data for this polymorph in the literature. We compare experimental NMR parameters with calculated values by the GIPAW DFT and dispersion corrected DFT-D2 methods. We found that while the computed 13C chemical shifts are generally in excellent agreement with experimental values, the quality of the computed 1H and 17O NMR chemical shifts is less satisfactory. This may imply that it is necessary to include the nuclear quantum effects in future quantum chemical calculations to account for potential proton tunneling and dynamics.

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Crystallography and NMR: Applications to Organic and Pharmaceutical Chemistry

Cited by 6 publications

References 75 publications

Exploiting NMR spectroscopy for the study of disorder in solids

Exploiting NMR spectroscopy for the study of disorder in solids

Engineering Codrug Solid Forms: Mechanochemical Synthesis of an Indomethacin–Caffeine System

Solid-State ¹H, ¹³C, and ¹⁷O NMR Characterization of the Two Uncommon Polymorphs of Curcumin

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Crystallography and NMR: Applications to Organic and Pharmaceutical Chemistry

Cited by 6 publications

References 75 publications

Exploiting NMR spectroscopy for the study of disorder in solids

Exploiting NMR spectroscopy for the study of disorder in solids

Engineering Codrug Solid Forms: Mechanochemical Synthesis of an Indomethacin–Caffeine System

Solid-State 1H, 13C, and 17O NMR Characterization of the Two Uncommon Polymorphs of Curcumin

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Solid-State ¹H, ¹³C, and ¹⁷O NMR Characterization of the Two Uncommon Polymorphs of Curcumin